Inflammation and the osteogenic regulation of vascular calcification: a review and perspective - PubMed (original) (raw)

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Inflammation and the osteogenic regulation of vascular calcification: a review and perspective

Jian-Su Shao et al. Hypertension. 2010 Mar.

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Figure 1. Inflammation and Osteogenic Regulation of Vascular Calcification: A Review and Working Model

Osteochondrocytic cells that promote vascular matrix mineralization can arise from at least two sources: (1) trans-differentiation of VSMCs – i.e., a type of phenotypic modulation in which the mature VSMC phenotype is replaced, and reprogrammed to that of an osteochondrocytic cell; or (2) osteogenic lineage allocation from a multipotent mesenchymal progenitor – i.e., a cell that has the potential to become an osteoblast, chondrocyte, VSMC, or adipocyte. Both processes are triggered by key inflammatory cytokines and oxidative stress signaling (boxed). VSMCs also elaborate apoptotic bodies and matrix vesicles that can nucleate mineral deposition – but also may play a role in removing vascular calciprotein particles via fetuin and MGP-dependent cellular uptake. Thus, apoptosis of VSMC not only provides substrate for nucleation, but also loss of cellular defenses. Multiple paracrine inhibitors control (a) pro-osteogenic signals provided by BMP/Wnt signaling, RANKL and TNF actions; and (b) nucleation/aggregation/epitaxial propagation of apatitic calcium phosphate deposition. Via HSP70-mediated inhibition of MGP and AKP2-mediated PPi degradation, inflammatory cytokines such as IL6 and TNF impair MGP and PPi defense mechanisms, respectively. Inflammation also down-regulates expression of serum fetuin, an import hepatocyte-derived inhibitor of soft tissue mineral deposition. Not shown are the enzymatic defense mechanisms such as catalase and glutathione peroxidase that reduce vascular oxidative stress, , . Although clearly an important stimulus for vascular BMP2 expression, remarkably few studies have examined the molecular mechanisms whereby hypertension activates vascular osteogenic signaling cascades. Of note, contribution of marrow-derived osteogenic endothelial progenitor cells as an additional source of mineralizing vascular mesenchymal progenitors has been recently posited, but has yet to be established. See text for details and additional references.

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